This invention relates generally to medical instrumentation and appliances and, in particular, to a temperature sensor catheter.
Arteriosclerosis is a major source of adult morbidity and mortality in industrialized countries. The condition may lead to a number of complications, including coronary thrombosis, myocardial ischemia, unstable angina, myocardial infarction and restenosis of stents and bypass grafts. The classification of atherosclerotic lesions by type can be valuable in predicting clinical complications, and the type of plaque is likely a better predictor of cardiovascular events than angiographic data.
Unstable plaque is well established as producing high risk for sudden myocardial infarction, either through plaque rupture and subsequent thrombotic response, or thrombosis generated at the inflamed surface of the plaque. The rupture of unstable plaque, and the subsequent generation of thrombus, has been estimated to account for 60 to 70% of fatal myocardial infarctions and up to 85% of all myocardial infarctions.
Unstable plaque is characterized by a lipid-rich core, chronic inflammation, fibrous cap, and activated macrophages. Angiography can identify the presence of a ruptured plaque after rupture, but often not before rupture. Thus, it cannot determine the risk associated with a given plaque.
Due to chronic inflammation, the temperature of unstable plaque is typically elevated above that of the adjacent sites on the inner lumen of the vessel. Extensive research has been conducted to confirm the elevated temperatures of unstable plaques, and to develop techniques to clinically identify them. It has been found that there is a correlation between the temperature of atherosclerotic plaque and the vulnerability to blood vessel rupture. In particular, it has been determined that inflamed, unstable deposits typically give off more heat than do healthy, non-inflamed tissues. Accordingly, there have been various apparatus and methods proposed to monitor the temperature of the vessel wall without occluding blood flow. U.S. Pat. Nos. 5,871,449; 5,924,997; and 5,935,075 provide background with regard to the general approach.
To determine that thrombotic events could be predicted through thermal measurements on the plaque surface, Willerson et al. measured the intimal surface temperatures on 20 sites located on 50 samples of excised living carotid artery samples from 48 patients using a thermistor, and then conducted histological studies. The results showed 37% of plaque regions warmer by up to 2.2xc2x0 C. These warmer regions could not be distinguished from cooler regions by visual observation, but correlated positively with cell density, a marker of inflammation.
Stefanadis et al. conducted human in vivo measurements of plaques using a Betatherm Microchip NTC 100K6 MCD368, 0.457 mm diameter thermistor on the end of a guidewire pressed against the vessel wall by a hydrofoil. They measured thermal heterogeneity of plaque temperatures repeatedly with an accuracy of 0.05xc2x0 C. and spatial and temporal resolutions of 500 um and 300 ms, in 90 patients with normal coronary arteries, stable angina, unstable angina, and with acute myocardial infarction. This group found artery-wall temperatures that increased progressively from normal patients, to stable angina patients, to unstable angina patients. The measurement of temperature differences in the inner lumen of coronary arteries shows great promise for identifying sites of unstable plaque.
Research on classification of plaque as stable or unstable has been carried out in three main areas: thermal, Ultra-Fast Magnetic Resonance Imaging (MRI) and Intravascular Ultrasound (IVUS), with some work on a few others (e.g. Raman scattering, Optical Coherence Tomography). While MRI and IVUS show promise, only thermal techniques offer a direct, inexpensive method of plaque classification that, due to its minimal hardware and disposable requirements, can be quickly and inexpensively implemented.
Plaque classification by MRI presents numerous obstacles. It brings the problems of requiring a special machine, typically located in other regions of the facility and not available on an ad hoc basis, into the cath lab as questions of plaque stability may arise. The ability of MRI to characterize human atherosclerotic plaque has been investigated by comparing MRI images of carotid artery plaque with histologic examination of the specimens after carotidendarterectomy. The studies indicated that MRI can discriminate the presence of a lipid core and fibrous cap in the carotid artery. The ability of MRI to characterize plaque composition of coronary arteries in the beating human heart has not been demonstrated. Even if the technical challenges of spatial and temporal resolution are solved, the cost of imaging coronary arteries using MRI is likely to be substantial.
While IVUS can accurately identify arteriosclerosis in its early stages, it is much less effective in the classification of plaque by type. Further, IVUS requires expensive and large equipment that also must be brought into the cath lab when needed. The main limitations of IVUS are cost and risk to the patient. IVUS enjoys an installed base in many cath labs, unlike other competing technologies to classify plaque, but it is problematic in this application. IVUS is very operator dependent and typically has a 300 micron resolution, the thickness of the fibrous cap on unstable plaque. Thus, IVUS does not have the needed resolution to identify unstable plaque. Although numerous clinical studies have been performed with IVUS, there are very limited follow-up data to suggest that IVUS examination of a coronary artery can be used to predict the probability that a plaque will rupture.
Yamagishi et al. performed IVUS examination of 114 coronary plaques in 106 patients. During an average follow-up period of 22 months, 12 patients had an acute coronary event related to a plaque that was previously examined by IVUS. Ten of the 12 plaques contained an echolucent zone consistent with a lipid-rich core. Only 4 of 90 sites not associated with acute events had an echolucent zone (p less than 0.05).
Optical Coherence Tomography (OCT) has problems due to its limited penetration distance, and the fact that it requires a saline flush to remove blood from the area and permit transmission of the optical radiation. Further, it can run only at xcx9c5 frames/sec, which will not give good time resolution. This technique, and others, such as pulsed laser radiation and the use of Raman scattering spectroscopy, require the vessel be purged of blood with clear saline for the signals to propagate. Further, they are much less developed than other techniques.
Classification of atherosclerotic plaque stability by measurement of its surface temperature is direct. Due to the chronic inflammation, the surface temperature of unstable plaque is typically elevated above that of the adjacent sites on the inner lumen of the vessel. Measurements in vivo and ex vivo have been made of active plaque sites, with temperature differences from the adjacent normal artery wall ranging up to 2 to 3xc2x0 C. The equipment associated with thermal measurements may be small and inexpensive, thus easily portable between cath labs or available in all cath labs in a single facility, as opposed to Magnetic Resonance Imaging (MRI) and Intravascular Ultrasound (IVUS). Identification of unstable plaques would permit the cardiologist to decide on treatment on a site-by-site basis during a single catheter insertion.
There are numerous potential treatments for these unstable lesions, including anti-inflammatory and/or anti-microbial treatments, aggressive cholesterol lowering, and heating to generate apoptosis. Stenting techniques are influenced by the classification of the plaque being treated.
Currently, no diagnostic or imaging modality exists that can predict either plaque rupture, hemorrhaging into plaque or plaque erosion in the clinical setting. Hot plaque temperature measurements have been made in research labs and in a few clinical studies, but no such product now exists. Practical and accurate techniques are needed to identify unstable plaque sites in order for these treatment decisions to occur. As classification of plaques becomes established, other therapeutic techniques will develop.
This invention resides in a thermal sensing catheter (TSC) operative to perform localized temperature measurements, including variations and fluctuations when such measurements are compared to readings taken at different places or at different times. The instrument finds particular utility in detecting and isolating unstable plaque. In the preferred embodiment, miniaturized temperature sensors in the form of microthermistors are embedded into expandable presentation elements disposed at the distal end of the catheter. The sensors may then be deployed to measure the surface temperature of the inner wall of coronary arteries at multiple sites to identify sites of elevated temperature indicative of unstable plaque.
The presentation elements may assume different forms according to the invention, including a xe2x80x9chandxe2x80x9d type design and an alternate basket-type structure. In the sensing hand configuration, a plurality (preferably up to 8) of sensors are embedded in the sides of polymeric or metallic sensing arms, which expand out from the centerline of a catheter toward the inner vessel walls. An asymmetric encapsulation technique is preferably used to embed the sensors in close proximity against an outer wall of a sensing arm, while maintaining an insulative backing to reduce the effect of blood temperature on the backside of the arms excessively influencing plaque temperature measurements.
The entire catheter, with thermal sensors and presentation system are preferably disposable. The disposable catheter assembly interfaces to a nondisposable data box receiving signals from the sensing elements. In the preferred embodiment, the data box is a battery-powered, hand-held device, encased in a plastic housing about the size of a pocket calculator. The data box includes a port to which the catheter assembly connects, thereby making electrical contact for ground and the signal lines of each of the individual sensors. The connections from each sensing element are direct; however, in an alternative configuration multiplexing may be used to reduce the number of signal wires.
The data box includes a display to present the calibrated readings from the sensors, as well as memory capabilities to store data for later download through a port incorporated in the housing. The output of the data box is provided to a computer, preferably in real-time and through the same port, to permit full-screen display of the thermal data. In either mode, a full recording of a procedure will be saved for later analysis.